Alleviation of cadmium uptake in rice (Oryza sativa L.) by iron plaque on the root surface generated by Providencia manganoxydans via Fe(II) oxidation.

Iron plaque is believed to be effective in reducing the accumulation of heavy metals in rice. In this work, a known soil-derived Mn(II)-oxidizing bacterium, LLDRA6, which represents the type strain of Providencia manganoxydans, was employed to investigate the feasibility of decreasing cadmium (Cd) accumulation in rice by promoting the formation of iron plaque on the root surface. Firstly, the Fe(II) oxidation ability of LLDRA6 was evaluated using various techniques including Fourier Transform infrared spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, phenanthroline photometry, and FeS gel-stabilized gradient assays. Subsequently, the formation of iron plaque on the root surface by LLDRA6 was investigated under hydroponic and pot conditions. Finally, Cd concentrations were examined in rice with and without iron plaque through pot and paddy-field tests. The results showed that LLDRA6 played an efficient role in the formation of iron plaque on seedling roots under hydroponic conditions, generating 44.87 and 36.72 g kg- 1 of iron plaque on the roots of Huazhan and TP309, respectively. In pot experiments, LLDRA6 produced iron plaque exclusively in the presence of Fe(II). Otherwise, it solely generated biofilm on the root surface. Together with Fe(II), LLDRA6 effectively reduced the concentrations of Cd in Huazhan roots, straws and grains by 25%, 46% and 44%, respectively. This combination also demonstrated a significant decrease in the Cd concentrations of TP309 roots, straws and grains by 20%, 52% and 44%, respectively. The data from the Cd translocation factor indicate that obstruction of Cd translocation by iron plaque predominantly occurred during the root-to-straw stage. In paddy-field tests, the Cd concentrations of grains harvested from the combination treatment of LLDRA6 and Fe(II) exhibited a decline ranging from 40 to 53%, which fell below the maximum acceptable value for Cd in rice grains (0.2 mg kg- 1) as per the China national standard for food security (GB2762-2017). Meanwhile, the relevant phenotypic traits regarding the yield were not adversely affected. These findings have demonstrated that LLDRA6 can impede the uptake of Cd by rice in Cd-contaminated soils through the formation of iron plaque on roots, thus providing a promising safe Cd-barrier for rice production.

In situ imaging of intracellular miRNAs in tumour cells by branched hybridisation chain reaction.

The ability to visualise microRNA in situ is crucial for studying microRNAs, their microRNA-associated biological functions and disease diagnosis. Traditional fluorescence in situ hybridisation methods based on paraformaldehyde fixation of microRNAs suffer from release of microRNAs from cells, which limits the sensitivity of in situ hybridisation, making them unsuitable for the detection of small, low-abundance microRNAs. To reduce the loss, microRNAs were covalently cross-linked to proteins within cells by combining EDC and paraformaldehyde, and the target microRNA was used as the initiator chain for a branched hybridisation chain reaction to detect microRNA expression levels in situ. A simplified branched hybridisation chain reaction can be realised by coupling two hybridisation chain reaction circuits with a hairpin linker. Upon forming the primary hybridisation chain reaction product with extended sequence, this sequence reacts with the linker hairpin H3 to release the initiator sequence, resulting in the formation of numerous dendritic branched hybridisation chain reaction products. Imaging results show that this technique can detect microRNAs with high sensitivity and selectivity at both the single-cell and single-molecule levels. Compared with the traditional fluorescence in situ hybridisation technique, this method greatly improves the sensitivity and image resolution of in situ imaging detection. Therefore, we believe that the target-initiated branched hybridisation chain reaction based in situ detection method provides a reliable assay platform for analysing disease-related microRNA expression.

ARL13B promotes cell cycle through the sonic hedgehog signaling pathway to alleviate nerve damage during cerebral ischemia/reperfusion in rats.

Cerebral ischemia/reperfusion (CIRI) is a leading cause of death worldwide. A small GTPase known as ADP-ribosylation factor-like protein 13B (ARL13B) is essential in several illnesses. The role of ARL13B in CIRI remains unknown, though. A middle cerebral artery occlusion/reperfusion (MCAO/R) in rats as well as an oxygen-glucose deprivation/reoxygenation (OGD/R) models in PC12 cells were constructed. The neuroprotective effects of ARL13B against MCAO/R were evaluated using neurological scores, TTC staining, rotarod testing, H&E staining, and Nissl staining. To detect the expression of proteins associated with the SHH pathway and apoptosis, western blotting and immunofluorescence were employed. Apoptosis was detected using TUNEL assays and flow cytometry. There was increased expression of ARL13B in cerebral ischemia/reperfusion models. However, ARL13B knockdown aggravated CIRI nerve injury by inhibiting the sonic hedgehog (SHH) pathway. In addition, the use of SHH pathway agonist (SAG) can increased ARL13B expression, reverse the effects of ARL13B knockdown exacerbating CIRI nerve injury. ARL13B alleviated cerebral infarction and pathological injury and played a protective role against MCAO/R. Furthermore, ARL13B significantly increased the expression of SHH pathway-related proteins and the anti-apoptotic protein BCL-2, while decreased the expression of pro-apoptotic protein BAX, thus reducing apoptosis. The results from the OGD/R model in PC12 cells were consistent with those obtained in vivo. Surprisingly, we demonstrated that ARL13B regulates the cell cycle to protect against CIRI nerve injury. Our findings indicate that ARL13B protects against CIRI by reducing apoptosis through SHH-dependent pathway activation, and suggest that ARL13B plays a crucial role in CIRI pathogenesis.

Identification and bioactivity evaluation of twelve previously undescribed depsidone derivatives from Garcinia oligantha.

Phytochemical studies on the leaves and twigs of Garcinia oligantha Merr. led to the isolation of twelve previously undescribed depsidone derivatives (oliganthdepsidones A-L, 1-12). Their structures were elucidated by extensive spectroscopic analysis including 1H and 13C NMR, HSQC, HMBC and NOESY along with HRESIMS. The structures of oliganthdepsidones G and J were finally determined using DFT-NMR chemical shift calculations and DP4+ methods. Cytotoxicity test in four human cancer cell lines indicated that oliganthdepsidone F had relatively strong cytotoxic effect against A375 (melanoma), A549 (lung cancer), HepG2 (liver cancer), and MCF-7 (breast cancer) cell lines with IC50 of 18.71, 15.44, 10.92, and 15.90 µM, respectively. The dose- and time-dependent antiproliferative effects of oliganthdepsidone F on these cell lines were also observed by CCK-8 test. As determined by fluorescent microscopy and flow cytometry in these cell lines, oliganthdepsidone F could promote cell apoptosis, leading to the inhibition of cell proliferation. The results of wound healing assay and transwell assay showed that oliganthdepsidone F could inhibit the migration and invasion of A549 and MCF-7 cell lines in a concentration-dependent manner.

Microplastic dilemma: Assessing the unexpected trade-offs between biodegradable and non-biodegradable forms on plant health, cadmium uptake, and sediment microbial ecology.

Despite extensive substitution of biodegradable plastics (BPs) for conventional plastics (CPs), research on their environmental ecological consequences as microplastics (MPs) is scarce. This study aimed to fill this gap by investigating the impacts of six prototypical MPs (categorized into BMPs and CMPs) on plant growth, cadmium (Cd) translocation, and bacterial communities in contaminated sediments. Results showed both BMPs and CMPs hindered plant development; yet interestingly, BMPs provoked more pronounced physiological and biochemical changes alongside increased oxidative stress due to reactive oxygen species accumulation. Notably, most MP types promoted the absorption of Cd by plant roots potentially via a "dilution effect". BMPs also induced larger shifts in soil microbial metabolic functions compared to CMPs. Ramlibacter was identified as a key biomarker distinguishing BMPs from CMPs, with link to multiple N metabolic pathways and N assimilation. This study offers novel insights into intricate biochemical mechanisms and environmental chemistry behaviors underpinning MP-Cd interactions within the plant-microbe-sediment system, emphasizing BMPs' higher potential ecological risks based on their significant effects on plant health and microbial ecology. This work contributes to enhancing the comprehensive understanding of their ecological implications and potential threats to environmental security.

Iron Plaque: A Shield against Soil Contamination and Key to Sustainable Agriculture.

Soils play a dominant role in supporting the survival and growth of crops and they are also extremely important for human health and food safety. At present, the contamination of soil by heavy metals remains a globally concerning environmental issue that needs to be resolved. In the environment, iron plaque, naturally occurring on the root surface of wetland plants, is found to be equipped with an excellent ability at blocking the migration of heavy metals from soils to plants, which can be further developed as an environmentally friendly strategy for soil remediation to ensure food security. Because of its large surface-to-volume porous structure, iron plaque exhibits high binding affinity to heavy metals. Moreover, iron plaque can be seen as a reservoir to store nutrients to support the growth of plants. In this review, the formation process of iron plaque, the ecological role that iron plaque plays in the environment and the interaction between iron plaque, plants and microbes, are summarized.

Design and Synthesis of Marine Polybrominated Diphenyl Ether Derivatives as Potential Anti-Inflammatory Agents.

Natural polybrominated diphenyl ethers are generally isolated from sponges and possess a broad range of biological activities. Through screening of our marine natural product library, we discovered that polybrominated diphenyl ethers 5 and 6 exhibit considerable anti-inflammatory activity. In order to expand our repertoire of derivatives for further biological activity studies, we designed and synthesized a series of 5-related polybrominated diphenyl ethers. Importantly, compound 5a showed comparable anti-inflammatory activity while much lower cytotoxicity on lipopolysaccharide (LPS)-induced RAW264.7 cells. Additionally, western blotting analysis showed that 5a reduced the expression of phosphorylated extracellular signal-regulated kinase (p-ERK). Besides, molecular docking experiments were conducted to predict and elucidate the potential mechanisms underlying the varying anti-inflammatory activities exhibited by compounds 5a, 5, and 6.

Doped Cu0 and sulfidation induced transition from R-O• to •OH in peracetic acid activation by sulfidated nano zero-valent iron-copper.

Peracetic acid (PAA) has emerged as a new effective oxidant for various contaminants degradation through advanced oxidation process (AOP). In this study, sulfidated nano zero-valent iron-copper (S-nZVIC) with low Cu doping and sulfidation was synthesized for PAA activation, resulting in more efficient degradation of sulfamethoxazole (SMX, 20 µM) and other contaminants using a low dose of catalyst (0.05 g/L) and oxidant (100 µM). The characterization results suggested that S-nZVIC presented a more uniform size and distribution with fewer metal oxides, as the agglomeration and oxidation were inhibited. More significantly, doped Cu0 and sulfidation significantly enhanced the generation and contribution of •OH but decreased that of R-O• in S-nZVIC/PAA/SMX system compared with that of nZVIC and S-nZVI, accounting for the relatively high degradation efficiency of 97.7% in S-nZVIC/PAA/SMX system compared with 85.7% and 78.9% in nZVIC/PAA/SMX and S-nZVI/PAA/SMX system, respectively. The mechanisms underlying these changes were that (i) doped Cu° could promote the regeneration of Fe(Ⅱ) for strengthened PAA activation through mediating Fe(Ⅱ)/Fe(Ⅲ) cycle by Cu(Ⅰ)/Cu(Ⅱ) cycle; (ii) S species might consume part of R-O•, resulting in a decreased contribution of R-O• in SMX degradation; (iii) sulfidation increased the electrical conductivity, thus facilitating the electron transfer from S-nZVIC to PAA. Consequently, the dominant reactive oxygen species transited from R-O• to •OH to degrade SMX more efficiently. The degradation pathways, intermediate products and toxicity were further analyzed through density functional theory (DFT) calculations, liquid chromatography-mass spectrometry (LC-MS) and T.E.S.T software analysis, which proved the environmental friendliness of this process. In addition, S-nZVIC exhibited high stability, recyclability and degradation efficiency over a wide pH range (3.0∼9.0). This work provides a new insight into the rational design and modification of nano zero-valent metals for efficient wastewater treatment through adjusting the dominant reactive oxygen species (ROS) into the more active free radicals.

Uterine Commensal Peptostreptococcus Species Contribute to IDO1 Induction in Endometrial Cancer via Indoleacrylic Acid.

Microbial dysbiosis has an increasingly appreciated impact on carcinogenesis, and the cervicovaginal microbiome plays a critical role in microenvironmental inflammation. Here, we investigated the involvement of the female genital tract Peptostreptococcus species in gynecological cancer via indoleacrylic acid (IAA). IAA production from Peptostreptococcus species and the effect of bacterial culture on tumor growth in vivo were examined. The impact of IAA on cytokine production and indoleamine-2,3-dioxygenase 1 (IDO1) expression in an endometrial cancer (EC) cell line, as well as their effect on Treg and Teff cells, and M1 and M2 macrophage populations were examined in EC patients and tumor-grafted mice. Clinically, Peptostreptococcus species abundance, IAA, and IDO1 expression were verified in EC patients. The results showed that IAA production was induced in the uteri of BALB/c nude mice by Peptostreptococcus species transplantation, and the intratumoral injection of a conditioned medium from Peptostreptococcus cultures into tumor-grafted mice promoted tumor growth. IL-10 expression was upregulated by IAA; IFN-γ expression was increased by IL-10. IFN-γ induced IDO1 expression in the EC cell line. The co-culture of IDO1-expressing EC cells with peripheral blood mononuclear cells upregulated the Treg proportion and decreased the M1/M2 ratio. Clinically, P. anaerobius was more abundant amongst the uterine microbiota of EC patients than the control. The IAA, IDO1, and kynurenine/tryptophan ratios were all higher in EC tissue, and the M1/M2 ratio was lower. Our study sheds light on the link between IDO1 induction and uterine Peptostreptococcus dysbiosis and provides a potential rationale for the role of Peptostreptococcus species in immune tolerance induction in type I endometrial cancer.

Xiebai San alleviates acute lung injury by inhibiting the phosphorylation of the ERK/Stat3 pathway and regulating multiple metabolisms.

BACKGROUND: Acute lung injury (ALI) often leads to serious respiratory diseases with high incidence rates and mortality. For centuries, Xiebai San (XBS) has been a classical traditional Chinese medicine (TCM) about respiratory illness such as pneumonia in children. However, the related mechanism of XBS against ALI remains indistinct. PURPOSE: To reveal specific targets of XBS in lipopolysaccharide (LPS)-induced ALI mice using integrated pharmacology. STUDY DESIGN: The integrated method was to expound mechanism and targets of XBS inhibited ALI. METHODS: The primary components in XBS were identified by ultra high performance liquid chromatography-quadrupole time of flight-mass spectrometry (UHPLC-QTOF-MS). The potential drug targets were established using network pharmacology. The anti-ALI effect of XBS was evaluated in mice. Additionally, therapeutic targets were screened by integrating metabolome and transcriptome and verified in lung tissue. RESULTS: In total, 163 chemical components were identified in XBS, and a network of "3 drugs-18 components-86 targets" for XBS against ALI was constructed. In ALI mice, XBS alleviated lung inflammation by decreasing permeation and expression of neutrophils, tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) in bronchoalveolar lavage fluid (BALF), serum, and lung tissue. Next, the transcriptome of lung tissue was analyzed and enriched, indicating the importance of mitogen-activated protein kinase (MAPK), Janus kinase-signal transducer and activator of transcription (JAK-STAT), and others, which was consistent with network pharmacology prediction. Also, western blotting and immunohistochemistry results showed that XBS was against ALI mainly by inhibiting extracellular signal regulated kinase (ERK) and signal transducer and activator of transcription 3 (Stat3) phosphorylation. In addition, the metabolome of lung tissue revealed that XBS mainly regulated pathways involved in arachidonic acid, glycerophospholipid, and tryptophan metabolisms. The expression levels of leukotriene, phosphatidylcholine, kynurenine, and others were also verified. CONCLUSION: XBS alleviated inflammation of ALI by inhibiting the phosphorylation of the ERK/Stat3 pathway and regulating arachidonic acid, glycerophospholipid, and tryptophan metabolisms. This study will guide clinical precision medicine and promote modernization of XBS.

High-solution emission characters and health risks of volatile organic compounds for sprayers in automobile repair industries.

The increasing automobile repair industries (ARIs) with spray facilities have become an important volatile organic compound (VOC) pollution source in China. However, the VOC health risk assessment for long-term exposure in ARIs has not been well characterized. In this study, though sampled VOCs from 51 typical ARIs in Beijing, the relationship between emission patterns, average daily exposure concentrations (EC), and health risks was comprehensively analyzed with the health assessment method. Results showed that concentrations of 117 VOCs from the samples ranged from 68.53 to 19863.32 µg·m-3, while the ARI operator's daily VOC inhalation EC was 11.24-1460.70 µg·m-3. The organic VOC (OVOC) concentration accounted for 73.16 ~ 94.52% in the solvent-based paint workshops, while aromatics were the main VOC component in water-based paint spraying (WPS) workshops, accounting for 70.08%, respectively. And the method of inhalation exposure health risk assessment was firstly used to evaluate carcinogenicity and non-carcinogenicity risk for sprayers in ARIs. The cumulative lifetime carcinogenic risk (LCR) for 24 sampled VOCs were within acceptable ranges, while the mean hazard index (HI) for 1 year with 44 sampled VOCs was over 1. Among them, ethyl alcohol had a high carcinogenic risk in both mixed water-based paint (MP) and solvent-based paint workshops. The mean HI associated with aromatics were 2.88E - 3 and 4.30E - 3 for 1 h in MP and WPS workshops. O-ethyl toluene and acetone are VOC components that need to be paid attention to in future paint raw materials and spraying operations. Our study will provide the important references for the standard of VOC occupational exposure health limits in ARIs.

Exploring novel Kokumi peptides in Agaricus bisporus: selection, identification, and tasting mechanism investigation through sensory evaluation and computer simulation analysis.

Agaricus bisporus contains amino acids associated with thickness and full-mouthfeel, making it a potential candidate for salt substitutes and flavor enhancers in various food applications. Kokumi peptides were isolated from the enzymatic digest of Agaricus bisporus using ultrafiltration nanofiltration, gel chromatographic separation, and RP-HPLC, coupled with sensory evaluation. Subsequently, the peptides, EWVPVTK and EYPPLGR, were selected for solid-phase synthesis based on molecular docking. Sensory analysis, including thresholds, time intensity, and dose-configuration relationships, indicated that EWVPVTK and EYPPLGR exhibited odor thresholds of 0.6021 mmol L-1 and 2.332 mmol L-1 in an aqueous solution. Molecular docking scores correlated with low sensory thresholds, signifying strong taste sensitivities. EWVPVTK, in particular, demonstrated a higher sense of richness at lower concentrations compared to EYPPLGR. Molecular docking and dynamics simulations elucidated that the interactions between Kokumi peptides and the CaSR receptor primarily involved hydrogen bonding, electrostatic interactions, and hydrophobic interactions. Both EWVPVTK and EYPPLGR exhibited stable binding to the CaSR receptor. Active binding sites were identified, with EWVPVTK interacting at Arg 66, Asp 216, Gln 245, and Asn 102, while EYPPLGR engaged with Ser 272, Gln 193, Glu 297, Ala-298, Tyr-2, and Agr-66 in hydrophilic interactions through hydrogen bonds. Notably, these two Kokumi peptides were found to be enriched in umami and sweet amino acids, underscoring their pivotal role in umami perception. This study not only identifies novel Kokumi peptides from Agaricus bisporus but also contributes theoretical foundations and insights for future studies in the realm of Kokumi peptides.

In vitro digestion and fecal fermentation of selenocompounds: impact on gut microbiota, antioxidant activity, and short-chain fatty acids.

Selenium bioavailability is critically influenced by gut microbiota, yet the interaction dynamics with selenocompounds remain unexplored. Our study found that L-Selenomethionine (SeMet) and Se-(Methyl)seleno-L-cysteine (MeSeCys) maintained stability during in vitro gastrointestinal digestion. In contrast, Selenite and L-Selenocystine (SeCys2) were degraded by approximately 13% and 35%. Intriguingly, gut microflora transformed MeSeCys, SeCys2, and Selenite into SeMet. Moreover, when SeCys2 and Selenite incubated with gut microbiota, they produced red selenium nanoparticles with diameters ranging between 100 and 400 nm and boosted glutathione peroxidase activity. These changes were positively associated with an increased relative abundance of unclassified_g__Blautia (Family Lachnospiraceae), Erysipelotrichaceae_UCG-003 (Family Erysipelatoclostridiaceae), and uncultured_bacterium_g__Subdoligranulum (Family Ruminococcaceae). Our findings implied that differential microbial sensitivities to selenocompounds, potentially attributable to their distinct mechanisms governing selenium uptake, storage, utilization, and excretion.

Rosmarinic Acid Liposomes Downregulate Hepcidin Expression via BMP6-SMAD1/5/8 Pathway in Mice with Iron Overload.

The objective of this study is to examine the potential protective effect of rosmarinic acid (RosA) encapsulated within nanoliposomes (RosA-LIP) on hepatic damage induced by iron overload. The characteristics, stability, and release of RosA-LIP in vitro were identified. The mice were randomly assigned to five groups: Control, Model, Model+DFO (DFO), Model+RosA (RosA), and Model+RosA-LIP (RosA-LIP). The iron overload model was induced by administering iron dextran (i.p.). The DFO, RosA, and RosA-LIP groups received iron dextran and were subsequently treated with DFO, RosA, and RosA-LIP for 14 days. We developed a novel formulation of RosA-LIP that exhibited stability and controlled release properties. Firstly, RosA-LIP improved liver function and ameliorated pathological changes in a mouse model of iron overload. Secondly, RosA-LIP demonstrated the ability to enhance the activities of T-SOD, GSH-Px, and CAT, while reducing the levels of MDA and 4-HNE, thereby effectively mitigating oxidative stress damage induced by iron overload. Thirdly, RosA-LIP reduced hepatic iron levels by downregulating FTL, FTH, and TfR1 levels. Additionally, RosA-LIP exerted a suppressive effect on hepcidin expression through the BMP6-SMAD1/5/8 signaling pathway. Furthermore, RosA-LIP upregulated FPN1 expression in both the liver and duodenum, thereby alleviating iron accumulation in these organs in mice with iron overload. Notably, RosA exhibited a comparable iron chelation effect, and RosA-LIP demonstrated superior efficacy in mitigating liver damage induced by excessive iron overload. RosA-LIP exhibited favorable sustained release properties, targeted delivery, and efficient protection against iron overload-induced liver damage. A schematic representation of the proposed protective mechanism of rosmarinic acid liposome during iron overload. Once RosA-LIP is transported into cells, RosA is released. On the one hand, RosA attenuates the BMP6-SMAD1/5/8-SMAD4 signaling pathway activation, leading to inhibiting hepcidin transcription. Then, the declined hepcidin contacted the inhibitory effect of FPN1 in hepatocytes and duodenum, increasing iron mobilization. On the other hand, RosA inhibits TfR1 and ferritin expression, which decreases excessive iron and oxidative damage.

Synergistic engineering of P, N-codoped carbon-confined bimetallic cobalt/nickel phosphides with tailored electronic structures for boosting urea electro-oxidation.

Bimetallic phosphides exhibit superior electrocatalytic activities and synergistic effects that make them ideal electrocatalysts for the urea oxidation reaction (UOR). Herein, P, N-codoped carbon-encapsulated cobalt/nickel phosphides derived from NiCo-MOF-74 (NiCoP@PNC) and anchored on P-doped carbonized wood fiber (PCWF) for UOR were prepared through synchronous carbonization and phosphorization. By benefiting from the synergistic effect of structural and electronic modulation, NiCoP@PNC/PCWF exhibits excellent UOR electrocatalytic performance under alkaline conditions, achieving a current density of 50 mA cm-2 with a potential of only 1.34 V (vs reversible hydrogen electrode, RHE) and continuous operation for more than 72 h. In addition, for the overall urea splitting, an electrolyzer using UOR replaced OER, which required only 1.50 V to achieve a current density of 50 mA cm-2 with excellent stability, 230 mV less than that required for the HER||OER system. In-depth theoretical analysis further proves that the strong synergistic effect between Co and Ni optimizes electronic structures, yielding excellent UOR properties. The synergistic strategy of structural and electrical modulation provides broad prospects for the design and synthesis of excellent UOR electrocatalysts for energy-saving hydrogen production by using renewable resources.

Elevated plasma FXII is associated with disease activity in ANCA-associated vasculitis: A Retrospective Cross-Sectional Study in Western China.

This study examined whether plasma FXII levels reflect disease activity in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Plasma FXII levels were detected by ELISA in 127 patients with AAV, and their associations with disease activity and plasma myeloperoxidase (MPO)-ANCA titre were examined. Immunofluorescent co-staining of FXII and neutrophils was performed on the renal tissues of patients with AAV. MPO expression in renal biopsy tissues was determined by immunohistochemical staining. The association between plasma FXII levels and histological activity was assessed in 82 patients who underwent kidney biopsy. Plasma FXII levels were considerably increased in patients with clinically active AAV compared to those in clinical remission and healthy individuals. Plasma FXII levels correlated positively with creatinine (r = 0.377), CRP (r = 0.222), urine red blood cell (r = 0.203), serum MPO-ANCA titer (r = 0.353), white blood cell (r = 0.194), percentage of glomeruli with crescents (P = 0.001), capillary breaks (P = 0.001), interstitial inflammation (P < 0.001) and fibrinoid necrosis (p < 0.001) on kidney biopsy. The plasma FXII optimal cut-off value for evaluating AAV activity was 24.5 µg/mL (sensitivity = 0.81, specificity = 0.82, P = 0.0001), which was superior to that achieved using conventional serologic biomarkers. Co-expression of FXII and neutrophils was higher, with increased MPO expression, in renal tissue with pathologically active AAV than that observed in pathologically inactive tissues. In conclusion, elevated plasma FXII levels reflect AAV clinical and histologic activity, and can serve as markers of active AAV.

Combination of the triglyceride-glucose index and EuroSCORE II improves the prediction of long-term adverse outcomes in patients undergoing coronary artery bypass grafting.

AIMS: We aimed to investigate the independent and combined association of the triglyceride-glucose (TyG) index and EuroSCORE II with major adverse cardiovascular event (MACE) after coronary artery bypass grafting (CABG), and examine whether the addition of the TyG index improves the predictive performance of the EuroSCORE II. MATERIALS AND METHODS: This study included 1013 patients who underwent CABG. The primary endpoint was MACE, which was defined as the composite of all-cause death, repeat coronary artery revascularisation, non-fatal myocardial infarction and non-fatal stroke. The patients were grouped by the TyG index and EuroSCORE II tertiles and the combination of these risk indicators. RESULTS: During the follow-up, 211 individuals developed MACE. Elevated levels of the TyG index and EuroSCORE II were associated with an increased risk of MACE. The hazard ratio [95% confidence interval (CI)] was 3.66 (2.34-5.73) in patients with the highest tertile of the TyG index and EuroSCORE II. Compared with the EuroSCORE II alone, combining the TyG index with EuroSCORE II achieved a better predictive performance [C-statistic increased 0.032, p < 0.001; continuous net reclassification improvement (NRI) (95% CI): 0.364 (0.215-0.514), p < 0.001; integrated discrimination improvement (IDI) (95% CI): 0.015 (0.007-0.023), p < 0.001, Akaike's information criteria (AIC) and Bayesian information criterion (BIC) decreased, and the likelihood ratio test, p < 0.001]. CONCLUSIONS: The TyG index and EuroSCORE II are independently associated with poor prognosis. Furthermore, the TyG index is an important adjunct to the EuroSCORE II for improving risk stratification and guiding early intervention among post-CABG patients.

Two pyrrole acids isolated from Phyllanthus emblica L. and their bioactivities.

An undescribed pyrrole acid, 1-(4'-methoxy-4'-oxobutyl)-1 H-pyrrole-2,5-dicarboxylic acid (1) and one known pyrrole acid (2) were isolated from the fruits of Phyllanthus emblica. The structures of these compounds were elucidated via the comprehensive analyses of IR, HRESIMS, 1D and 2D spectroscopic data. A series of biological assays revealed that compounds 1 and 2 could inhibit LPS-induced over-production of nitric oxide (NO), interleukin-6 (IL-6), monocyte chemotactic protein 1 (MCP-1) and tumor necrosis factor-α (TNF-α) by reducing the phosphorylation of extracellular regulated protein kinases (ERK) and c-Jun N-terminal kinases (JNK) in RAW 264.7 cells. Additionally, compounds 1 and 2 were found to reduce lipid deposition and increase the mRNA expression of ATP-binding cassette transporter A1 in oxidized low-density lipoprotein-treated RAW264.7 macrophages.

Triglyceride-glucose index in the prediction of adverse cardiovascular events in patients without diabetes mellitus after coronary artery bypass grafting: a multicenter retrospective cohort study.

BACKGROUND: The triglyceride-glucose (TyG) index has been evaluated as a reliable surrogate for insulin resistance (IR) and has been proven to be a predictor of poor outcomes in patients with cardiovascular diseases. However, data are lacking on the relationship of the TyG index with prognosis in nondiabetic patients who underwent coronary artery bypass grafting (CABG). Thus, the purpose of our current study was to investigate the potential value of the TyG index as a prognostic indicator in patients without diabetes mellitus (DM) after CABG. METHODS: This multicenter, retrospective cohort study involving 830 nondiabetic patients after CABG from 3 tertiary public hospitals from 2014 to 2018. Kaplan-Meier survival curve analysis was conducted followed by the log-rank test. Cox proportional hazards regression models were used to explore the association between the TyG index and major adverse cardiovascular events (MACEs). The incremental predictive power of the TyG index was evaluated with C-statistics, continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: An incrementally higher TyG index was associated with an increasingly higher cumulative incidence of MACEs (log-rank test, p < 0.001). The hazard ratio (95% CI) of MACEs was 2.22 (1.46-3.38) in tertile 3 of the TyG index and 1.38 (1.18-1.62) per SD increase in the TyG index. The addition of the TyG index yielded a significant improvement in the global performance of the baseline model [C-statistic increased from 0.656 to 0.680, p < 0.001; continuous NRI (95% CI) 0.269 (0.100-0.438), p = 0.002; IDI (95% CI) 0.014 (0.003-0.025), p = 0.014]. CONCLUSIONS: The TyG index may be an independent factor for predicting adverse cardiovascular events in nondiabetic patients after CABG.

The metabolic score for insulin resistance in the prediction of major adverse cardiovascular events in patients after coronary artery bypass surgery: a multicenter retrospective cohort study.

BACKGROUND: The metabolic score for insulin resistance (METS-IR) is a simple, convenient, and reliable marker for resistance insulin (IR), which has been regarded as a predictor of cardiovascular disease (CVD) and cardiovascular events. However, few studies examined the relationship between METS-IR and prognosis after coronary artery bypass graft (CABG). This study aimed to investigate the potential value of METS-IR as a prognostic indicator for the major adverse cardiovascular events (MACE) in patients after CABG. METHOD: 1100 CABG patients were enrolled in the study, including 760 men (69.1%) and 340 women (30.9%). The METS-IR was calculated as Ln [(2 × FPG (mg/dL) + fasting TG (mg/dL)] × BMI (kg/m2)/Ln [HDL-C (mg/dL)]. The primary endpoint of this study was the occurrence of major adverse cardiovascular events (MACE), including a composite of all-cause death, non-fatal myocardial infarction (MI), coronary artery revascularization, and stroke. RESULT: The following-up time of this study was 49-101 months (median, 70 months; interquartile range, 62-78 months). During the follow-up period, there were 243 MACEs (22.1%). The probability of cumulative incidence of MACE increased incrementally across the quartiles of METS-IR (log-rank test, p < 0.001). Multivariate Cox regression analysis demonstrated a hazard ratio (95% CI) of 1.97 (1.36-2.86) for MACE in quartile 4 compared with participants in quartile 1. The addition of the METS-IR to the model with fully adjusting variables significantly improved its predictive value [C-statistic increased from 0.702 to 0.720, p < 0.001, continuous net reclassification improvement (NRI) = 0.305, < 0.001, integrated discrimination improvement (IDI) = 0.021, p < 0.001]. CONCLUSION: METS-IR is an independent and favorable risk factor for predicting the occurrence of MACE and can be used as a simple and reliable indicator that can be used for risk stratification and early intervention in patients after CABG.